Our major objective is to enhance understanding of the ventilatory control system. A second objective is to enhance understanding of the general physiologic effects of chronic CO2 inhalation. To achieve these objectives, four specific studies will be completed on awake ponies. We will first determine the effect of sectioning the hilar branches of the vagus nerve (termed lung denervation, LD) on the Hering Breuer inflation reflex, and on ventilation (VE), respiratory timing, blood gases and pHa during eupnea, and during conditions of acute CO2 inhalation, acute hypoxia, muscular exercise and thermal stress. These studies, on 6 ponies before and 3 weeks after LD, should provide insight into the role of slowly adapting pulmonary stretch receptors in regulation of ventilation. The second study will be on 4-6 normal, 4-6 LD, and 4-6 carotid body denervated (CBD) ponies before, during and after 3 weeks of chronic exposure to 2 percent CO2. What is the relationship during chronic CO2 inhalation between VE and known or postulated VE stimulants (plasma and cerebrospinal fluid (CSF), PCO2, H+, morepinephrine, and NH3)? What is the effect of LD and CBD on the hyperpnea during chronic CO2 inhalation (which in other species is sustained in spite of normalization of [H+] in plasma and CSF)? What is the effect of chronic CO2 inhalation on body temperature, metabolic rate, systemic and pulmonary vascular pressures, and renal and endocrine functions that regulate blood volume and its composition? In the third study, we will determine the effect of L2 spinal lesions on the VE and cardiovascular responses to muscular exercise. Six ponies will exercise on a treadmill (4 legs, hindlegs only, and forelegs only) before and 2 weeks after partial lesioning of the dorsal lateral sulcus (DLS) and dorsal lateral funiculus (DLF). And finally we wish to determine whether occlusion, redundancy and/or plasticity exist within the ventilatory control system. If LD or spinal lesions alter ventilatory responses, then will these responses gradually return toward normal (as occurs following CBD)? Is the effect of a specific neurotomy (CBD, LD, DLS and DLF lesions) altered by a prior or a simultaneous lesion of a second receptor or neural pathway? In addition to providing insight into basic regulatory mechanisms, these studies are important because of the insight they should provide relative to patient care in situations where individual or multiple components of the ventilatory control system are chronically compromised.